The recent development of a rapid and sensitive assay for mitochondrial adenine nucleotide translocase (ANT) has made possible short term temporal studies on a single dog heart. These studies indicate that the inhibition of ANT by elevated levels of long chain acyl CoA esters (LCACAE) occurs within seconds of the onset of ischemia. Related studies have also shown that LCACAE inhibition of ANT causes a marked decrease in mitochondrial creatine phosphate production. Infusion of atractyloside, an ANT specific inhibitor, appears to cause an ischemic-like condition of the myocardium. These findings suggest that mitochondrial ANT inhibition by LCACAE may be the first enzyme system to be affected by the onset of ischemia. Investigations now underway seek to support these preliminary findings by means of a variety of biochemical, hemodynamic, and ultrastructural studies. Other studies in progress are aimed at pharmacological interventions which may alleviate cardiac ischemia by reversing LCACAE inhibition of mitochondrial ANT. BIBLIOGRAPHIC REFERENCES: Recent Advances in Studies on Cardiac Structure and Metabolism, Volume 10 - Metabolism of Contraction, ed. by P.E. Roy and G. Rona. University Park Press, Baltimore, 1976, (In press).